Study of the optimum level of electrode placement for the evaluation of absolute lung resistivity with the Mk3.5 EIT system.

Inter-subject variability has caused the majority of previous electrical impedance tomography (EIT) techniques to focus on the derivation of relative or difference measures of in vivo tissue resistivity. Implicit in these techniques is the requirement for a reference or previously defined data set. This study assesses the accuracy and optimum electrode placement strategy for a recently developed method which estimates an absolute value of organ resistivity without recourse to a reference data set. Since this measurement of tissue resistivity is absolute, in Ohm metres, it should be possible to use EIT measurements for the objective diagnosis of lung diseases such as pulmonary oedema and emphysema. However, the stability and reproducibility of the method have not yet been investigated fully. To investigate these problems, this study used a Sheffield Mk3.5 system which was configured to operate with eight measurement electrodes. As a result of this study, the absolute resistivity measurement was found to be insensitive to the electrode level between 4 and 5 cm above the xiphoid process. The level of the electrode plane was varied between 2 cm and 7 cm above the xiphoid process. Absolute lung resistivity in 18 normal subjects (age 22.6 +/- 4.9, height 169.1 +/- 5.7 cm, weight 60.6 +/- 4.5 kg, body mass index 21.2 +/- 1.6: mean +/- standard deviation) was measured during both normal and deep breathing for 1 min. Three sets of measurements were made over a period of several days on each of nine of the normal male subjects. No significant differences in absolute lung resistivity were found, either during normal tidal breathing between the electrode levels of 4 and 5 cm (9.3 +/- 2.4 Omega m, 9.6 +/- 1.9 Omega m at 4 and 5 cm, respectively: mean +/- standard deviation) or during deep breathing between the electrode levels of 4 and 5 cm (10.9 +/- 2.9 Omega m and 11.1 +/- 2.3 Omega m, respectively: mean +/- standard deviation). However, the differences in absolute lung resistivity between normal and deep tidal breathing at the same electrode level are significant. No significant difference was found in the coefficient of variation between the electrode levels of 4 and 5 cm (9.5 +/- 3.6%, 8.5 +/- 3.2% at 4 and 5 cm, respectively: mean +/- standard deviation in individual subjects). Therefore, the electrode levels of 4 and 5 cm above the xiphoid process showed reasonable reliability in the measurement of absolute lung resistivity both among individuals and over time.

Infective endocarditis in congenital heart disease: Japanese national collaboration study.

OBJECTIVE: To provide pure cohorts of paediatric and adult patients with congenital heart disease (CHD) and infective endocarditis (IE) for making future guidelines. DESIGN: Japanese nationwide survey. SETTING: 66 Japanese institutions. PATIENTS: 170 children, mean (SD) age 7.4 (5.7) years (range 14 days to 17 years), and 69 adults, age 32.5 (14.1) years (range 18-69) who developed IE between 1997 and 2001 (one in 240 admissions with CHD). MAIN OUTCOME MEASURES: Clinical presentation of IE. RESULTS: 119 patients including 88 with cyanotic CHD had previous cardiac surgery. Procedures preceding IE were dental (12%) followed by cardiovascular surgery (8%). Sites of infection were left sided in 46% and right sided in 51%. Vegetation with diameter of 11 mm was documented in 151 (63%). Frequent complications were embolic events (stroke 11%, other emboli 20%) and cardiac failure (23%). The most common microorganisms were streptococci (50%) and staphylococci (37%) with methicillin resistant Staphylococcus aureus in 7.5%. Empirical treatments were penicillins (alone or with other antibiotics 57%) followed by cephems (22%) and vancomycin (11%). Surgery during active IE was common (26%), with vegetation (45%) and heart failure (29%) as the most frequent indications. Mortality was 8.8%: 8.0% among patients who received medical treatment alone and 11.1% among those with active IE who underwent surgery. The causes of death (n = 21) were surgery (7), infection (7), cardiac failure (6), and renal failure (1). CONCLUSIONS: Because of a recent increase in the incidence of IE and high mortality and complication rate, it is mandatory to establish well formulated recommendations for management of IE in paediatric and adult patients with CHD based on a large cohort. Results of this nationwide multicentre database should be helpful in establishing guidelines.

Alleviation of myocardial ischemia after Kawasaki disease by heparin and exercise therapy.

BACKGROUND: Heparin promotes angiogenesis. We evaluated the effects of combined treatment with heparin and exercise on myocardial ischemia in the chronic stage of Kawasaki disease. METHODS AND RESULTS: This study was conducted in 7 patients (aged 6 to 19 years) who had a totally occluded coronary artery and stress-induced myocardial ischemia in the collateral-dependent areas. Twice-daily exercise using a bicycle ergometer was performed with increments of 0.5 W/kg every 3 minutes up to maximal exertion for 10 days. Heparin, which immediately increased circulating hepatocyte growth factor, was given intravenously 10 minutes before each exercise period. Newly developed myocardial infarction, ventricular tachyarrhythmia, anginal attack, or hemorrhagic complication was not observed in any patient. Dipyridamole-loading single photon emission computed tomography documented improved myocardial perfusion in the collateral-dependent areas and a significant reduction in total defect scores in all patients after the completion of 20 sessions (P=0.01). In control patients who did not receive the heparin-exercise therapy, however, stress defect scores remained unchanged (n=1) or increased (n=2) during follow-up. Computerized quantitative coronary angiography provided evidence that the heparin-exercise therapy increased the diameter of the occluded artery to which collaterals terminated (P=0.001) but not that of the reference artery with which collaterals were not connected (P=0.96). CONCLUSIONS: The findings suggest that a series of heparin and exercise treatments over 10 days may have a dramatic effect on the alleviation of myocardial ischemia in collateral-dependent regions. This may be a safe, noninvasive revascularization therapy for patients with coronary artery occlusion in the chronic stage of Kawasaki disease.

Expression of tumor necrosis factor-alpha protein in the myocardium in fatal myocarditis.

BACKGROUND: Tumor necrosis factor (TNF)-alpha is the most studied cytokine in the failing human heart and in experimental murine myocarditis. We have investigated the expression of TNF-alpha in the myocardium in human myocarditis. METHODS: We examined endomyocardial biopsy (n = 4) and autopsy (n = 5) tissues obtained from nine patients diagnosed with myocarditis by the Dallas criteria. Expression of TNF-alpha in the hearts was immunohistochemically studied using monoclonal antibodies against human TNF-alpha. RESULTS: Tumor necrosis factor-alpha protein was expressed in the myocardium of six of the nine patients studied. Four of five fatal patients showed intense immunoreactivity for TNF-alpha compared with survivors. Furthermore, left ventricular systolic function was reduced in patients with TNF-alpha-positive hearts. CONCLUSIONS: These findings may support the suggestion that TNF-alpha plays an important role in cardiac dysfunction and myocytic damage in fatal human myocarditis.

Dramatic decrease of circulating levels of monocyte chemoattractant protein-1 in Kawasaki disease after gamma globulin treatment.

Kawasaki disease (KD) is a systemic vasculitis preferentially affecting coronary arteries. Extensive monocytes/macrophages infiltrate in the vascular lesions, implying the involvement of a chemotactic cytokine in their recruitment. We investigated the role of monocyte chemoattractant protein-1 (MCP-1, also termed monocyte chemotactic and activating factor) in KD. In the immunohistochemical studies using the cardiac tissues of patients with fatal KD, MCP-1 but not interleukin (IL) -8 or macrophage inflammatory protein-1alpha was localized at the extracellular matrix associated with mononuclear cellular infiltration. The sites of MCP-1 expression correlated with the distribution of the acute inflammation, including early coronary vasculitis. In prospectively studied patients with KD, circulating levels of MCP-1, IL-8, tumor necrosis factor alpha (TNF-alpha), and IL-1alpha were elevated in 73, 77, 57, and 0% of samples before gamma globulin (GG) treatment (400 mg/kg x 5 days = total 2 g/kg), respectively, compared with respective control values. GG treatment correlated with a rapid decrease in the circulating levels of MCP-1 (P = 0.001) but not IL-8 (P = 0.19) or TNF-alpha (P = 0.33). In the sensitive Western blotting, MCP-1 bound to GG. Furthermore, GG inhibited the MCP-1-induced Ca2+ influx in a human monocytic cell line in vitro. These findings suggest a role of MCP-1 in KD, and indicate that GG treatment may block MCP-1 activity, thus alleviating KD vasculitis.

Vascular endothelial growth factor in acute Kawasaki disease.

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is an important regulator of angiogenesis and blood vessel permeability. Kawasaki disease (KD) is characterized by systemic vasculitis with increased vascular permeability, implying a possible role of VEGF in KD. To elucidate the involvement of VEGF in the pathogenesis of KD, we investigated 30 patients with acute KD, comparing the time course of plasma VEGF levels (n = 123) with clinical symptoms and laboratory findings. Compared with control values, the peak levels of plasma VEGF were significantly elevated (38+/-26 vs 244+/-248 pg/ml, p <0.001). The VEGF levels at the appearance of skin rash and/or edema of hands and feet were also elevated to 176+/-163 pg/ml (p <0.001). In 7 patients (23%), the plasma VEGF levels remained increased after the resolution of the skin rash and peripheral edema. The VEGF levels were independent of gamma globulin therapy and levels of serum albumin and C-reactive protein. We also measured the plasma levels of transforming growth factor-beta1 (TGF-beta1) and tumor necrosis factor alpha, both of which can upregulate VEGF in vitro. The plasma levels of VEGF were highly correlated with those of TGF-beta1 (n = 63, r = 0.73, p <0.001) but not with those of tumor necrosis factor alpha. These findings suggest that the production of VEGF is increased and may be upregulated by TGF-beta1 in acute KD. VEGF may be involved in the hyperpermeability of local blood vessels in acute KD.

Survey for Trypanosoma cruzi infection in a municipality in northeast Brazil.

An epidemiological survey of Trypanosoma cruzi infection was carried out in Bodocó, located in the western part of the State of Pernambuco, Brazil. Two hundred and forty-one individuals were parasitologically and immunologically screened. Although hemoculture did not reveal the presence of parasites in the blood, the sera of 5 individuals were scored as positive by the indirect fluorescence antibody test and the enzyme-linked immunosorbent assay. Seropositivity in individuals above and below the age of 40 was 14.8 and 0.5%, respectively. These results indicate that recent infections with T. cruzi are rare in this area. However, since a T. cruzi-infected triatomid (Triatoma brasiliensis) was captured in a school classroom, this area must be considered endemic. When triatomid feces containing parasites were inoculated into a jird (mongolian gerbil), parasitemia appeared 10 days later. Immunohistochemical staining, using monoclonal antibody specific for T. cruzi, labeled organisms in jird tissues. These observations demonstrate that the jird is a suitable host for experimental T. cruzi infections and that monoclonal antibody is effective for detection of the parasite in host tissues.

Occurrence of a community with high morbidity associated with Schistosoma mansoni infection regardless of low infection intensity in north-east Brazil.

To establish the relationship between schistosome-associated morbidity and infection intensity in northeast Brazil, a parasitological and ultrasonographical study was carried out on 484 inhabitants of 4 villages (I, II, III and IV) in São Lourenço da Mata, Pernambuco, Brazil, where schistosomiasis is endemic. Quantitative stool examination using Knight's method demonstrated a high prevalence and moderate intensity of Schistosoma mansoni infection, and also that the subjects in village IV had a significantly lower prevalence and intensity of infection than those of the other villages. By ultrasonography, periportal fibrosis (PPF) and splenomegaly were found in 52% of the 299 infected subjects and 66% of the 146 infected subjects aged over 16 years old, respectively; 32% and 31% of the 299 infected subjects had abnormally high values of total bile acid (TBA) and alkaline phosphatase (ALP) activity, respectively. Liver and spleen size, PPF, and serum level of TBA and ALP were not correlated with infection intensity. There was no significant difference in the morbidity assessed by liver and spleen size, PPF, and serum analysis between the subjects in village IV and the other villages. These findings suggest the occurrence of a community with high morbidity associated with schistosomiasis regardless of low infection intensity.

Dietary fish oil supplementation exacerbates serum sickness nephritis in mice.

The effects of fish oil (FO) on immune complex nephritis induced by bovine serum albumin (BSA) were studied in female B10.Br mice. The mice were fed an experimental fat-free diet composed of either 10% FO, safflower oil (SO), or beef tallow (BT) as a lipid source throughout the study. Proteinuria was observed in 84% of the FO group (n = 19), 53% of the SO group (n = 19) and in 48% of the BT group (n = 19; p = 0.0217 vs. FO). The FO group showed a tendency toward more severe renal histologic changes than the SO and BT groups. The levels of anti-BSA antibody and circulating BSA-anti-BSA immune complexes were significantly higher in the FO group than in the SO and in the BT groups. Avidity of the anti-BSA antibodies showed a lower tendendy in the FO group. Prostaglandin E2 and thromboxane B2 productions by the renal cortex were much lower in the FO than in the other two groups. The ratios thromboxane B2/prostaglandin E2 were higher in the FO than in the BT group. These results suggest that FO oil supplementation leads to the deterioration of BSA-induced immune complex nephritis in mice due to the altered immune responses in association with suppressed prostanoid production.

Validation of the proximal isovelocity surface area method for assessing mitral regurgitation in children.

The proximal isovelocity surface area (PISA) method for calculating volume flow through the regurgitant orifice has attracted significant attention. A number of in vitro studies and clinical studies in adults suggest that the method is accurate. However, when applying the method to children it must be noted that the absolute regurgitation volume is small, and the range of body sizes is wide. This study investigated the accuracy of the PISA method for quantitative assessment of the severity of mitral regurgitation in children. Twenty children aged 7 months to 12 years (average 4.7 years) with mitral regurgitation but without interventricular shunt or aortic stenosis were selected for this study. Underlying cardiac diseases included atrioventricular septal defects in nine, isolated mitral regurgitation in five, and association with other heart defects in six. The PISA radius (r) and the duration of regurgitation (T) were measured on color M-mode recordings, with the M line passing through the center of the PISA. Assuming that the PISA is a hemisphere, maximal regurgitant flow rate (MFR: ml/s) was calculated as MFR = 2pi x r2 x V (r = maximal radius, V = aliasing velocity), and regurgitant stroke volume (RSVpisa) as RSVpisa = 2pi x MSR x V x T (MSR = mean square of the PISA radius during regurgitation). As a validating standard, total stroke volume (TSV) using two-dimensional echocardiography determined by the area-length volumetry method and forward stroke volume (FSV) by the pulsed Doppler method were measured, and regurgitant stroke volume (RSVD: RSVD = TSV - FSV) and regurgitant fraction (RF: RF = RSVD/TSV) were calculated. A linear correlation was found between MFR, RSVpisa, and RSVD (X) (MFR = 4.2X + 54.0, r = 0.84. RSVpisa = 1. 0X + 9.8, r = 0.90), and both RSVpisa and MFR divided by body surface area (BSA: m2) revealed a significant correlation with regurgitant fraction (X) by nonlinear regression analysis (RSVpisa/BSA = 26.2 x X/(1 - X) + 16.8, r = 0.85. MFR/BSA = 121.8 x X/(1 - X) + 92.2, r = 0.79). It is concluded that maximal regurgitant flow rate, regurgitant stroke volume, and regurgitant fraction can be accurately predicted in children using the PISA method by Doppler echocardiography.

Molecular and functional properties of cytochrome c from adult Ascaris suum muscle.

Mitochondrial cytochrome c was isolated at high purity from adult Ascaris suum muscle and its molecular properties were investigated. The molecular weight of A. suum cytochrome c was determined to be 13,119 by electrospray ionization mass spectrometry. The oxidation-reduction potential of nematode cytochrome c was measured to be +248 mV; this value is comparable to those for cytochrome c from mammalian sources. The A. suum cytochrome c, like bovine heart cytochrome c, showed biphasic kinetics against bovine heart cytochrome c oxidase. Comparative kinetic studies revealed species-specificity in the reaction between cytochrome c and cytochrome c oxidase from A. suum and bovine sources. The cytochrome c content in mitochondria was highest at the second larval stage, in which the respiratory chain is the most aerobic among various developmental stages of A. suum. These data clearly show that adult A. suum cytochrome c, as isolated, is a bona fide substrate for cytochrome c oxidase in the aerobic respiratory chain of second-stage larvae.

Measurement of ventricular volumes by cine magnetic resonance imaging in complex congenital heart disease with morphologically abnormal ventricles.

This study assessed the validity of cine magnetic resonance imaging (MRI) for measuring right and left ventricular volumes by using Simpson's rule in children with complex congenital heart disease. Forty-five patients with complex congenital heart disease (average age 2.6 years) and 10 controls (average age 2.3 years) were evaluated. The whole heart was encompassed by contiguous transverse sections. Ventricular volumes were calculated by adding luminal areas determined in each section at end diastole and end systole. End-diastolic and end-systolic volumes by MRI in both groups correlated well with those by ventriculography (r>0.89). Comparison of the ejection fraction in both ventricles in both groups yielded a good correlation between MRI and ventriculography (r>0.67). MRI technique in both groups had low intraobserver and interobserver variation (<6%). Cine MRI provides a suitable noninvasive means of quantifying ventricular volume in children with complex congenital heart disease.